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银杏二萜内酯葡胺注射液调控缺血性脑卒中急性期血小板生成与活化的作用机制

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中草药 | 药理与临床 2026,57(10): 3818-3830

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中草药 |药理与临床 2026 , 57 (10) : 3818 -3830

银杏二萜内酯葡胺注射液调控缺血性脑卒中急性期血小板生成与活化的作用机制

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戴文静¹, 吕文欣¹, 詹乐¹, 颜昌钖¹, 武子寅¹, 赵宾江¹, 曹亮¹, 肖伟¹, 孙雨琴¹, 王振中¹

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通讯作者:

孙雨琴

作者简介:

戴文静: 戴文静(2001—),女,硕士研究生,研究方向为药物制剂与产品研发。E-mail:dwj01191202@163.com

Mechanism of Diterpene Ginkgolides Meglumine Injection in regulating platelet production and activation during acute phase of ischemic stroke

DAI Wenjing, LYU Wenxin, ZHAN Le, YAN Changyang, WU Ziyin, ZHAO Binjiang, CAO Liang, XIAO Wei, SUN Yuqin, WANG Zhenzhong

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doi: 10.7501/j.issn.0253-2670.2026.10.013

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目的基于血小板的生成与活化探讨银杏二萜内酯葡胺注射液（Diterpene Ginkgolides Meglumine Injection，DGMI）治疗缺血性脑卒中（ischemic stroke，IS）急性期的作用机制。方法设置假手术组、模型组、伊布替尼（10 mg/kg）组和DGMI低、中、高剂量（6.25、12.50、25.00 mg/kg）组，采用线栓法制备C57BL/6小鼠短暂性大脑中动脉栓塞（transient middle cerebral artery occlusion，tMCAO）模型，术后0.5 h开始给药，连续给药3 d。采用2,3,5-氯化三苯基四氮唑（2,3,5-triphenyltetrazolium chloride，TTC）染色测定脑梗死率；采用转棒实验和Bederson评分评估运动及神经功能；采用流式细胞术和ELISA分别检测全血血小板数量与血清中血小板因子4（platelet factor 4，PF4）水平；采用骨髓涂片和免疫组化观察骨髓巨核细胞的增殖、分化、凋亡以及黏着斑激酶（focal adhesion kinase，FAK）的磷酸化水平；采用免疫荧光染色检测脑组织内血小板的激活和FAK的磷酸化水平。另设置FAK激动剂ZINC40099027（ZIN）与中剂量DGMI联用组，验证DGMI是否通过抑制FAK激活发挥保护作用。结果 DGMI能显著减轻tMCAO小鼠脑梗死和巨核细胞生成，其中，中剂量DGMI对tMCAO小鼠骨髓巨核细胞的分化与增殖的抑制作用以及对脑梗死面积的减少、运动协调能力和神经功能评分的改善作用最为明显（P＜0.05、0.01、0.001）。此外，DGMI能显著减少tMCAO小鼠血小板的数量和血清中PF4水平（P＜0.05、0.001），并抑制骨髓巨核细胞和脑内浸润血小板中FAK的磷酸化（P＜0.01、0.001）。FAK激动剂ZIN显著逆转了DGMI对tMCAO小鼠的上述保护作用（P＜0.05、0.01、0.001）。结论 DGMI通过抑制IS急性期巨核细胞过度生成和脑内浸润血小板中FAK的磷酸化，进而抑制血小板的生成和活化，最终发挥脑保护作用。

关键词

银杏二萜内酯葡胺注射液 / 缺血性脑卒中 / 血小板 / 巨核细胞 / 黏着斑激酶

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Objective To explore the mechanism of Diterpene Ginkgolides Meglumine Injection (银杏二萜内酯葡胺注射液, DGMI) in treatment of acute ischemic stroke (IS) based on platelet generation and activation. Methods Sham group, model group, ibrutinib (10 mg/kg) group, DGMI low-, medium- and high-dose (6.25, 12.50, 25.00 mg/kg) groups were established. A transient middle cerebral artery occlusion (tMCAO) model was prepared in C57BL/6 mice using suture method. Medication was administered continuously for 3 d starting 0.5 h after surgery. The infarct rate was measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Motor and neurological function were evaluated using spinning rod experiment and Bederson score. Flow cytometry and ELISA were used to detect the whole blood platelet count and platelet factor 4 (PF4) level in serum. Bone marrow smears and immunohistochemistry were used to observe the proliferation, differentiation, apoptosis and phosphorylation levels of focal adhesion kinase (FAK) in bone marrow megakaryocytes. Immunofluorescence staining was used to detect platelet activation and FAK phosphorylation levels in brain tissue. A combination group of FAK agonist ZINC40099027 (ZIN) and medium-dose DGMI was set up to verify whether DGMI exerts a protective effect by inhibiting FAK activation. Results DGMI significantly reduced cerebral infarction and megakaryocyte generation in tMCAO mice. Among them, the inhibitory effect of medium-dose DGMI on differentiation and proliferation of bone marrow megakaryocytes in tMCAO mice, as well as the improvement of cerebral infarction area, motor coordination ability and neurological function score were the most significant (P < 0.05, 0.01, 0.001). In addition, DGMI could significantly reduce the number of platelets and PF4 level in serum of tMCAO mice (P < 0.05, 0.001), and inhibit the phosphorylation of FAK in bone marrow megakaryocytes and infiltrating platelets in brain (P < 0.01, 0.001). The FAK agonist ZIN significantly reversed the protective effects of DGMI on tMCAO mice (P < 0.05, 0.01, 0.001). Conclusion DGMI exerts neuroprotective effects by inhibiting the excessive generation of megakaryocytes during the acute phase of IS and the phosphorylation of FAK in infiltrating platelets in the brain, thereby suppressing platelet generation and activation.

Key words

Diterpene Ginkgolides Meglumine Injection / ischemic stroke / platelet / megakaryocyte / focal adhesion kinase

引用本文

戴文静, 吕文欣, 詹乐, 颜昌钖, 武子寅, 赵宾江, 曹亮, 肖伟, 孙雨琴, 王振中. 银杏二萜内酯葡胺注射液调控缺血性脑卒中急性期血小板生成与活化的作用机制. 中草药, 2026 , 57 (10) : 3818 -3830 . DOI: 10.7501/j.issn.0253-2670.2026.10.013

DAI Wenjing, LYU Wenxin, ZHAN Le, YAN Changyang, WU Ziyin, ZHAO Binjiang, CAO Liang, XIAO Wei, SUN Yuqin, WANG Zhenzhong. Mechanism of Diterpene Ginkgolides Meglumine Injection in regulating platelet production and activation during acute phase of ischemic stroke[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (10) : 3818 -3830 . DOI: 10.7501/j.issn.0253-2670.2026.10.013

基金

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癌症、心脑血管、呼吸和代谢性疾病防治研究国家科技重大专项 (2024ZD0522100); 中药制药过程控制与智能制造技术全国重点实验室重点项目 (SKL2023D01001); 基因组学研究建设平台 (SKL2023D01009)

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2026年第57卷第10期

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doi: 10.7501/j.issn.0253-2670.2026.10.013

接收时间：2026-01-13
首发时间：2026-09-09

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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